The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation ...The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.展开更多
Objective：The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods：Cultured human larynge...Objective：The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods：Cultured human laryngeal cancer cellline Hep-2 and human vascular endothelial cells in vitro, cells got into the period of exponential phase of growth, was diviced into 3 groups：group I （control group）, group II （DDP group）, group III （Rg3 group）. Added to the Hep-2 cells Rg3 and DDP, made Rg3 final concentration was 300μg/mL, and DDP was 3μg/mL. 48 h later, specimens from sample to be done immunocytochemistry, and the protein of VEGF in Hep-2 cells to be detected. Col ecting Hep-2 cells supernatant, some was used to measure the protein level of VEGF in Hep-2 cells supernatant by ELISA. Some was used to culture HVEC. 24 h later, cellgrowth inhibition rate of human vascular endothelial was determined by MTT. Results：The protein level of VEGF was evi-dently higher in group I compared to group II and group III, it was not only in Hep-2 cells, but also in supernatant of Hep-2 cells. There was no significantly dif erent between group II and group III. MTT results showed that, the human vascular endothelial cellgrowth inhibition rate of group I was significantly lower than that of group II and group III （P〈0.05）. At the same time the HVEC growth inhibition rate of group II was significantly lower than that of group III （P〈0.05）. Conclusion：The inhibition to tumor angiogenesis of Rg3 is stronger than traditional chemotherapy drug cisplatin. It worke by reducing the biological ef ects of secreted VEGF, But the ef ecting worke by reducing the activity of secreted VEGF itself or af ecting endothelial function of VEGF receptor or some other ways to be further studied.展开更多
To investigate the molecular mechanism of leptin regulating insulin secretion through determining the regulation of insulin secretion and the insulin receptor substrate (IRS)-2-associated phosphoinositide 3-kinase (PI...To investigate the molecular mechanism of leptin regulating insulin secretion through determining the regulation of insulin secretion and the insulin receptor substrate (IRS)-2-associated phosphoinositide 3-kinase (PI3K) activity by leptin in the isolated rat pancreatic islets, pancreatic islets were isolated from male SD rats by the collagenase method. The purified islets were incubated with leptin 2 nmol/L for 1 h in the presence of 5.6 mmol/L or 11.1 mmol/L glucose. Insulin release was measured using radioimmunoassay. IRS-2-associated activity of PI3K was determined by immunoprecipitate assay and Western blot. The results showed that in the presence of 5.6 mmol/L glucose, leptin had no significant effect on both insulin secretion and IRS-2-associated PI3K activity, but in the presence of 11.1 mmol/L glucose, insulin release was significantly inhibited after the islets were exposed to leptin for 1 h (P<0.01). PI3K inhibitor wortmannin blocked the inhibitory regulation of leptin on insulin release (P<0.05). Western Blot assay revealed that 2 nmol/L leptin could significantly increase the IRS-2-associated activity of PI3K by 51.5 % (P<0.05) in the presence of 11.1 mmol/L glucose. It was concluded that Leptin could significantly inhibit insulin secretion in the presence of 11.1 mmol/L glucose by stimulating IRS-2-associated activity of PI3K, which might be the molecular mechanism of leptin regulating insulin secretion.展开更多
AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secre...AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.展开更多
Objective To investigate the value of BT-H3 in expressed prostatic secretions ( EPS) in differential diagnosis of patients with inflammatory elevation of PSA in t - PSA gray zone ( 4 - 10 ng /ml) . Methods One hundred...Objective To investigate the value of BT-H3 in expressed prostatic secretions ( EPS) in differential diagnosis of patients with inflammatory elevation of PSA in t - PSA gray zone ( 4 - 10 ng /ml) . Methods One hundred and sixteen patients from ages of 19 to 80 years ( mean,40 years) were studied. In the group there展开更多
目的探究经介入治疗后,急性心肌梗死(AMI)患者血清分泌型卷曲相关蛋白2(SFRP2)、血管生成素样蛋白3(ANGPTL3)水平表达情况及其与左心室重构和主要心血管不良事件(MACE)的关系。方法选取2023年3月至2024年5月于石家庄市急救中心网络医院...目的探究经介入治疗后,急性心肌梗死(AMI)患者血清分泌型卷曲相关蛋白2(SFRP2)、血管生成素样蛋白3(ANGPTL3)水平表达情况及其与左心室重构和主要心血管不良事件(MACE)的关系。方法选取2023年3月至2024年5月于石家庄市急救中心网络医院进行介入治疗的AMI患者103例,根据1年后是否发生MACE分为非MACE组(79例)和MACE组(24例)。比较两组一般临床资料,左心室重构指标[包括左心房内径(LAD)、左心室舒张末期内径(LVEDD)和左心室射血分数(LVEF),左心室质量指数(LVMI)];采用Pearson相关分析血清SFRP2、ANGPTL3与左心室重构指标的相关性;采用ROC曲线分析血清SFRP2、ANGPTL3对AMI患者发生MACE的预测价值;采用相对危险度分析SFRP2、ANGPTL3高低表达患者MACE发生风险。结果两组年龄、性别、吸烟、饮酒、高血压、糖尿病、AMI分型、收缩压、舒张压、身体质量指数比较,差异无统计学意义(P>0.05)。与非MACE组比较,MACE组LAD[(43.58±4.62)mm vs(34.51±3.65)mm]、LVEDD[(56.84±5.94)mm vs(45.81±4.92)mm]、LVMI(156.23±18.91 vs 108.95±11.65)升高,LVEF降低[(45.26±4.92)%vs(62.15±6.48)%],差异有统计学意义(P<0.05)。Pearson相关分析显示,血清SFRP2与LAD、LVEDD、LVMI呈负相关(r=-0.526、-0.524、-0.538,P<0.001),与LVEF呈正相关(r=0.531,P<0.001);血清ANGPTL3与LAD、LVEDD、LVMI呈正相关(r=0.498、0.501、0.532,P<0.001),与LVEF呈负相关(r=-0.528,P<0.05)。血清SFRP2、ANGPTL3预测AMI患者发生MACE的AUC分别为0.867、0.853,两者联合预测AMI患者发生MACE的AUC为0.951,优于血清SFRP2、ANGPTL3单独预测(Z=2.624,P=0.009;Z=2.447,P=0.014)。结论AMI患者血清SFRP2水平降低、ANGPTL3水平升高,与患者左心室重构指标具有一定相关性,对评估MACE发生具有一定辅助预测价值。展开更多
Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.H...Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.展开更多
基金the grants from the National Natural Science Foundation of China(U1805232,31770156,and 32172365)the China Postdoctoral Science Foundation(2021M690637)。
文摘The fine-tuned expression dynamics of the effector genes are pivotal for the transition from vegetative growth to host colonization of pathogenic filamentous fungi.However,mechanisms underlying the dynamic regulation of these genes remain largely unknown.Here,through comparative transcriptome and chromatin immunoprecipitation sequencing(ChIP-seq)analyses of the methyltransferase PoKmt6 in rice blast fungus Pyricularia oryzae(syn.Magnaporthe oryzae),we found that PoKmt6-mediated H3K27me3 deposition was enriched mainly at fast-evolving regions and contributed to the silencing of a subset of secreted proteins(SP)and transposable element(TE)families during the vegetative growth of P.oryzae.Intriguingly,we observed that a group of SP genes,which were depleted of H3K27me3 modification,could also be silenced via the H3K27me3-mediated repression of the nearby TEs.In conclusion,our results indicate that H3K27me3 modification mediated by PoKmt6 regulates the expression of some SP genes in fast-evolving regions through the suppression of nearby TEs.
文摘Objective：The aim of this study was to investigate the af ecting of Rg3 to secreted VEGF of human laryngeal carcinoma Hep-2 cells and its mechanism of inhibition to tumor angiogenesis. Methods：Cultured human laryngeal cancer cellline Hep-2 and human vascular endothelial cells in vitro, cells got into the period of exponential phase of growth, was diviced into 3 groups：group I （control group）, group II （DDP group）, group III （Rg3 group）. Added to the Hep-2 cells Rg3 and DDP, made Rg3 final concentration was 300μg/mL, and DDP was 3μg/mL. 48 h later, specimens from sample to be done immunocytochemistry, and the protein of VEGF in Hep-2 cells to be detected. Col ecting Hep-2 cells supernatant, some was used to measure the protein level of VEGF in Hep-2 cells supernatant by ELISA. Some was used to culture HVEC. 24 h later, cellgrowth inhibition rate of human vascular endothelial was determined by MTT. Results：The protein level of VEGF was evi-dently higher in group I compared to group II and group III, it was not only in Hep-2 cells, but also in supernatant of Hep-2 cells. There was no significantly dif erent between group II and group III. MTT results showed that, the human vascular endothelial cellgrowth inhibition rate of group I was significantly lower than that of group II and group III （P〈0.05）. At the same time the HVEC growth inhibition rate of group II was significantly lower than that of group III （P〈0.05）. Conclusion：The inhibition to tumor angiogenesis of Rg3 is stronger than traditional chemotherapy drug cisplatin. It worke by reducing the biological ef ects of secreted VEGF, But the ef ecting worke by reducing the activity of secreted VEGF itself or af ecting endothelial function of VEGF receptor or some other ways to be further studied.
基金This project was supported by Ministry of Education Re-turning Overseas Scholar science study Foundation( 2 0 0 2 2 47) ,province Hubei Natural Sciences Foundation( 2 0 0 2 AB13 6) ,Wuhan science and Technology ChenguangPlan Foundation( 9910 0 2 0 9)
文摘To investigate the molecular mechanism of leptin regulating insulin secretion through determining the regulation of insulin secretion and the insulin receptor substrate (IRS)-2-associated phosphoinositide 3-kinase (PI3K) activity by leptin in the isolated rat pancreatic islets, pancreatic islets were isolated from male SD rats by the collagenase method. The purified islets were incubated with leptin 2 nmol/L for 1 h in the presence of 5.6 mmol/L or 11.1 mmol/L glucose. Insulin release was measured using radioimmunoassay. IRS-2-associated activity of PI3K was determined by immunoprecipitate assay and Western blot. The results showed that in the presence of 5.6 mmol/L glucose, leptin had no significant effect on both insulin secretion and IRS-2-associated PI3K activity, but in the presence of 11.1 mmol/L glucose, insulin release was significantly inhibited after the islets were exposed to leptin for 1 h (P<0.01). PI3K inhibitor wortmannin blocked the inhibitory regulation of leptin on insulin release (P<0.05). Western Blot assay revealed that 2 nmol/L leptin could significantly increase the IRS-2-associated activity of PI3K by 51.5 % (P<0.05) in the presence of 11.1 mmol/L glucose. It was concluded that Leptin could significantly inhibit insulin secretion in the presence of 11.1 mmol/L glucose by stimulating IRS-2-associated activity of PI3K, which might be the molecular mechanism of leptin regulating insulin secretion.
文摘AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.
文摘Objective To investigate the value of BT-H3 in expressed prostatic secretions ( EPS) in differential diagnosis of patients with inflammatory elevation of PSA in t - PSA gray zone ( 4 - 10 ng /ml) . Methods One hundred and sixteen patients from ages of 19 to 80 years ( mean,40 years) were studied. In the group there
文摘目的探究经介入治疗后,急性心肌梗死(AMI)患者血清分泌型卷曲相关蛋白2(SFRP2)、血管生成素样蛋白3(ANGPTL3)水平表达情况及其与左心室重构和主要心血管不良事件(MACE)的关系。方法选取2023年3月至2024年5月于石家庄市急救中心网络医院进行介入治疗的AMI患者103例,根据1年后是否发生MACE分为非MACE组(79例)和MACE组(24例)。比较两组一般临床资料,左心室重构指标[包括左心房内径(LAD)、左心室舒张末期内径(LVEDD)和左心室射血分数(LVEF),左心室质量指数(LVMI)];采用Pearson相关分析血清SFRP2、ANGPTL3与左心室重构指标的相关性;采用ROC曲线分析血清SFRP2、ANGPTL3对AMI患者发生MACE的预测价值;采用相对危险度分析SFRP2、ANGPTL3高低表达患者MACE发生风险。结果两组年龄、性别、吸烟、饮酒、高血压、糖尿病、AMI分型、收缩压、舒张压、身体质量指数比较,差异无统计学意义(P>0.05)。与非MACE组比较,MACE组LAD[(43.58±4.62)mm vs(34.51±3.65)mm]、LVEDD[(56.84±5.94)mm vs(45.81±4.92)mm]、LVMI(156.23±18.91 vs 108.95±11.65)升高,LVEF降低[(45.26±4.92)%vs(62.15±6.48)%],差异有统计学意义(P<0.05)。Pearson相关分析显示,血清SFRP2与LAD、LVEDD、LVMI呈负相关(r=-0.526、-0.524、-0.538,P<0.001),与LVEF呈正相关(r=0.531,P<0.001);血清ANGPTL3与LAD、LVEDD、LVMI呈正相关(r=0.498、0.501、0.532,P<0.001),与LVEF呈负相关(r=-0.528,P<0.05)。血清SFRP2、ANGPTL3预测AMI患者发生MACE的AUC分别为0.867、0.853,两者联合预测AMI患者发生MACE的AUC为0.951,优于血清SFRP2、ANGPTL3单独预测(Z=2.624,P=0.009;Z=2.447,P=0.014)。结论AMI患者血清SFRP2水平降低、ANGPTL3水平升高,与患者左心室重构指标具有一定相关性,对评估MACE发生具有一定辅助预测价值。
基金the financial support from the National Key Research and Development Program of China(No.2023YFD1701100)the National Natural Science Foundation of China(No.32072450)+2 种基金the National Science Fund for Distinguished Young Scholars of Guangdong Province(No.2021B1515020107)the Opening Foundation of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology(No.NRG202306)the Opening Foundation of Guangdong Province Key Laboratory of Microbial Signals and Disease Control(No.MSDC2023-19)。
文摘Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.
